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A Colloid Approach to Self-Assembling Antibodies

Skar-Gislinge, Nicholas; Ronti, Michela; Garting, Tommy LU ; Rischel, Christian; Schurtenberger, Peter LU ; Zaccarelli, Emanuela and Stradner, Anna LU (2019) In Molecular Pharmaceutics 16(6). p.2394-2404
Abstract

Concentrated solutions of monoclonal antibodies have attracted considerable attention due to their importance in pharmaceutical formulations; yet, their tendency to aggregate and the resulting high viscosity pose considerable problems. Here we tackle this problem by a soft condensed matter physics approach, which combines a variety of experimental measurements with a patchy colloid model, amenable of analytical solution. We thus report results of structural antibodies and dynamic properties obtained through scattering methods and microrheological experiments. We model the data using a colloid-inspired approach, explicitly taking into account both the anisotropic shape of the molecule and its charge distribution. Our simple patchy model... (More)

Concentrated solutions of monoclonal antibodies have attracted considerable attention due to their importance in pharmaceutical formulations; yet, their tendency to aggregate and the resulting high viscosity pose considerable problems. Here we tackle this problem by a soft condensed matter physics approach, which combines a variety of experimental measurements with a patchy colloid model, amenable of analytical solution. We thus report results of structural antibodies and dynamic properties obtained through scattering methods and microrheological experiments. We model the data using a colloid-inspired approach, explicitly taking into account both the anisotropic shape of the molecule and its charge distribution. Our simple patchy model is able to disentangle self-assembly and intermolecular interactions and to quantitatively describe the concentration-dependence of the osmotic compressibility, collective diffusion coefficient, and zero shear viscosity. Our results offer new insights on the key problem of antibody formulations, providing a theoretical and experimental framework for a quantitative assessment of the effects of additional excipients or chemical modifications and a prediction of the resulting viscosity.

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Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
antibodies, patchy colloids, self-assembly
in
Molecular Pharmaceutics
volume
16
issue
6
pages
11 pages
publisher
The American Chemical Society
external identifiers
  • scopus:85066118810
ISSN
1543-8384
DOI
10.1021/acs.molpharmaceut.9b00019
language
English
LU publication?
yes
id
98961cbf-9159-4157-aaa1-609a7c92417f
date added to LUP
2019-06-14 13:46:05
date last changed
2019-07-02 04:48:08
@article{98961cbf-9159-4157-aaa1-609a7c92417f,
  abstract     = {<p>Concentrated solutions of monoclonal antibodies have attracted considerable attention due to their importance in pharmaceutical formulations; yet, their tendency to aggregate and the resulting high viscosity pose considerable problems. Here we tackle this problem by a soft condensed matter physics approach, which combines a variety of experimental measurements with a patchy colloid model, amenable of analytical solution. We thus report results of structural antibodies and dynamic properties obtained through scattering methods and microrheological experiments. We model the data using a colloid-inspired approach, explicitly taking into account both the anisotropic shape of the molecule and its charge distribution. Our simple patchy model is able to disentangle self-assembly and intermolecular interactions and to quantitatively describe the concentration-dependence of the osmotic compressibility, collective diffusion coefficient, and zero shear viscosity. Our results offer new insights on the key problem of antibody formulations, providing a theoretical and experimental framework for a quantitative assessment of the effects of additional excipients or chemical modifications and a prediction of the resulting viscosity.</p>},
  author       = {Skar-Gislinge, Nicholas and Ronti, Michela and Garting, Tommy and Rischel, Christian and Schurtenberger, Peter and Zaccarelli, Emanuela and Stradner, Anna},
  issn         = {1543-8384},
  keyword      = {antibodies,patchy colloids,self-assembly},
  language     = {eng},
  number       = {6},
  pages        = {2394--2404},
  publisher    = {The American Chemical Society},
  series       = {Molecular Pharmaceutics},
  title        = {A Colloid Approach to Self-Assembling Antibodies},
  url          = {http://dx.doi.org/10.1021/acs.molpharmaceut.9b00019},
  volume       = {16},
  year         = {2019},
}